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Ovarian hormones elicit phosphorylation of akt and extracellular-signal regulated kinase in explants of the cerebral cortex

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Abstract

Estradiol and progesterone both have been demonstrated to afford neuroprotection against various insults. In an attempt to identify potential mechanisms underlying these neuroprotective effects, two key elements within signal transduction pathways linked to neuroprotection were evaluated. In mouse cerebral cortical explants, both estradiol and progesterone elicited the phosphorylation of Akt, a downstream effector of the phosphoinositide-3 (PI-3) kinase pathway. Progesterone also elicited the phosphorylation of extracellular-signal regulated kinase (ERK), a component of the mitogen-activated protein kinase (MAPK) pathway. These effects were not inhibited by the progesterone receptor antagonist, RU486. However, inhibition of either MAPK/ERK kinase with PD98059 or PI-3 kinase with LY294002 successfully inhibited progesterone's actions on ERK and Akt, respectively. Collectively, the data offer novel mechanisms for both progesterone and estrogen action in the central nervous system, demonstrating the functional and mechanistic diversity of gonadal hormones and supporting their neuroprotective potential for such neurodegenerative disorders as Alzheimer disease.

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References

  1. Toran-Allerand, C. D. (1976). Brain Res. 106, 407–412.

    Article  PubMed  CAS  Google Scholar 

  2. Toran-Allerand, C. D. (1980). Brain Res. 189, 413–427.

    Article  PubMed  CAS  Google Scholar 

  3. Luine, V. N., Richards, S. T., Wu, V. Y., and Beck, K. D. (1998). Horm. Behav. 34, 149–162.

    Article  PubMed  CAS  Google Scholar 

  4. Singh, M., Meyer, E. M., Millard, W. J., and Simpkins, J. W. (1994). Brain Res. 644, 305–312.

    Article  PubMed  CAS  Google Scholar 

  5. Panickar, K. S., Guan, G., King, M. A., Rajakumar, G., and Simpkins, J. W. (1997). J. Neurobiol. 33, 961–967.

    Article  PubMed  CAS  Google Scholar 

  6. Singer, C. A., Rogers, K. L., Strickland, T. M., and Dorsa, D. M. (1996). Neurosci. Lett. 212, 13–16.

    Article  PubMed  CAS  Google Scholar 

  7. Green, P. S., Gridley, K. E., and Simpkins, J. W. (1996). Neurosci. Lett. 218, 165–168.

    Article  PubMed  CAS  Google Scholar 

  8. Gridley, K. E., Green, P. S., and Simpkins, J. W. (1997). Brain Res. 778, 158–165.

    Article  PubMed  CAS  Google Scholar 

  9. Goodman, Y., Bruce, A. J., Cheng, B., and Mattson, M. P. (1996). J. Neurochem. 66, 1836–1844.

    Article  PubMed  CAS  Google Scholar 

  10. Simpkins, J. W., Rajakumar, G., Zhang, Y. Q., Simpkins, C. E., Greenwald, D., Yu, C. J., Bodor, N., and Day, A. L. (1997). J. Neurosurg. 87, 724–730.

    Article  PubMed  CAS  Google Scholar 

  11. Hawk, T., Zhang, Y. Q., Rajakumar, G., Day, A. L., and Simpkins, J. W. (1998). Brain Res. 796, 296–298.

    Article  PubMed  CAS  Google Scholar 

  12. Behl, C., Widmann, M., Trapp, T., and Holsboer, F. (1995). Biochem. Biophys. Res. Commun. 216, 473–482.

    Article  PubMed  CAS  Google Scholar 

  13. Roof, R. L., Duvdevani R., Braswell, L., and Stein, D. G. (1994). Exp. Neurol. 129, 64–69.

    Article  PubMed  CAS  Google Scholar 

  14. Asbury, E. T., Fritts, M. E., Horton, J. E., and Isaac, W. L. (1998). Behav. Brain Res. 97, 99–106.

    Article  PubMed  CAS  Google Scholar 

  15. Roof, R. L., Hoffman, S. W., and Stein, D. G. (1997). Mol. Chem. Neuropathol. 31, 1–11.

    PubMed  CAS  Google Scholar 

  16. Landers, J. P. and Spelsberg, T. C. (1992). Crit. Rev. Eukaryot. Gene Expr. 2 19–63.

    PubMed  CAS  Google Scholar 

  17. Gronemeyer, H. (1992). FASEB J. 6, 2524–2529.

    PubMed  CAS  Google Scholar 

  18. Aronica, S. M., Kraus, W. L., and Katzenellenbogen, B. S. (1994). Proc. Natl. Acad. Sci. USA 91, 8517–8521.

    Article  PubMed  CAS  Google Scholar 

  19. Beyer, C. and Karolczak, M. (2000). J. Neurosci. Res. 59, 107–116.

    Article  PubMed  CAS  Google Scholar 

  20. Watters, J. J. and Dorsa, D. M. (1998). J. Neurosci. 18, 6672–6680.

    PubMed  CAS  Google Scholar 

  21. Morley, P., Whitfield, J. F., Vanderhyden, B. C., Tsang, B. K., and Schwartz, J. L. (1992). Endocrinology 131, 1305–1312.

    Article  PubMed  CAS  Google Scholar 

  22. Pozzo-Miller, L. D., Inoue, T., and Murphy, D. D. (1999). J. Neurophysiol. 81, 1404–1411.

    PubMed  CAS  Google Scholar 

  23. Buitrago, C., Massheimer, V., and de Boland, A. R. (2000). Cell Signal 12, 47–52.

    Article  PubMed  CAS  Google Scholar 

  24. Migliaccio, A., Di Domenico, M., Castoria G., de Falco A., Bontempo, P., Nola, E., and Auricchio, F. (1996). EMBO J. 15, 1292–1300.

    PubMed  CAS  Google Scholar 

  25. Singer, C. A., Figueroa-Masot, X. A., Batchelor, R. H., and Dorsa, D. M. (1999). J. Neurosci. 19, 2455–2463.

    PubMed  CAS  Google Scholar 

  26. Singh, M., Setalo, G. Jr., Guan, X., Warren, M., and Toran-Allerand, C. D. (1999). J. Neurosci. 19, 1179–1188.

    PubMed  CAS  Google Scholar 

  27. Singh, M., Setalo, G. Jr., Guan, X., Frail, D. E., and Toran-Allerand, C. D. (2000). J. Neurosci. 20, 1694–1700.

    PubMed  CAS  Google Scholar 

  28. Desdouits-Magnen, J., Desdouits, F., Takeda, S., Syu, L. J., Saltiel, A. R., Buxbaum, J. D., Czernik, A. J., Nairn, A. C., and Greengard, P. (1998). J. Neurochem. 70, 524–530.

    Article  PubMed  CAS  Google Scholar 

  29. Mills, J., Laurent Charest, D., Lam, F., Beyreuther, K., Ida, N., Pelech, S. L., and Reiner, P. B. (1997). J. Neurosci. 17, 9415–9422.

    PubMed  CAS  Google Scholar 

  30. Datta, S. R., Brunet, A., and Greenberg, M. E. (1999). Genes Dev. 13, 2905–2927.

    Article  PubMed  CAS  Google Scholar 

  31. Datta, S. R., Dudek, H., Tao, X., Masters, S., Fu, H., Gotoh, Y., and Greenberg, M. E. (1997). Cell 91, 231–241.

    Article  PubMed  CAS  Google Scholar 

  32. Zha, J., Harada H., Yang, E., Jockel, J., and Korsmeyer, S. J. (1996). Cell 87, 619–628.

    Article  PubMed  CAS  Google Scholar 

  33. D'Mello, S. R., Borodezt, K., and Soltoff, S. P. (1997). J. Neurosci. 17, 1548–1560.

    PubMed  Google Scholar 

  34. Klesse, L. J. and Parada, L. F. (1998). J. Neurosci. 18, 10,420–10,428.

    CAS  Google Scholar 

  35. Dudek, H., Datta, S. R., Franke, T. F., Bimbaum, M. J., Yao, R., Cooper, G. M., Segal, R. A., Kaplan, D. R., and Greenberg, M. E. (1997). Science 275, 661–665.

    Article  PubMed  CAS  Google Scholar 

  36. Marshall, C. (1995). Cell 80, 179–185.

    Article  PubMed  CAS  Google Scholar 

  37. Jung-Testas, I., Do Thi, A., Koenig, H., Desarnaud, F., Shazand, K., Schumacher, M., and Baulieu, E. E. (1999). J. Steroid Biochem. Mol. Biol. 69, 97–107.

    Article  PubMed  CAS  Google Scholar 

  38. Jung-Testas, I. and Baulieu, E. E. (1998). J. Steroid Biochem. Mol. Biol. 65, 243–251.

    Article  PubMed  CAS  Google Scholar 

  39. Szeberenyi, J. (1996). Neurobiology (Budapest) 4, 1–11.

    CAS  Google Scholar 

  40. Vanhoutte, P., Barnier, J. V., Guibert, B., Pages, C., Besson, M. J., Hipskind, R. A., and Caboche, J. (1999). Mol. Cell. Biol. 19, 136–146.

    PubMed  CAS  Google Scholar 

  41. Whitmarsh, A. J., Shore, P., Sharrocks, A. D., and Davis, R. J. (1995). Science 269, 403–407.

    Article  PubMed  CAS  Google Scholar 

  42. Xing, J., Kornhauser, J. M., Xia, Z., Thiele, E. A., and Greenberg, M. E. (1998). Mol. Cell. Biol. 18, 1946–1955.

    PubMed  CAS  Google Scholar 

  43. Sgambato, V., Pages, C., Rogard, M., Besson, M. J., and Caboche, J. (1998). J. Neurosci. 18, 8814–8825.

    PubMed  CAS  Google Scholar 

  44. Szeberenyi, J. and Erhardt, P. (1994). Biochim. Biophys. Acta 1222, 187–202.

    Article  PubMed  CAS  Google Scholar 

  45. Davis, R. J. (1995). Mol. Reprod. Dev. 42, 459–467.

    Article  PubMed  CAS  Google Scholar 

  46. Frodin, M., and Gammeltoft, S. (1999). Mol. Cell. Endocrinol. 151, 65–77.

    Article  PubMed  CAS  Google Scholar 

  47. Nguyen, T. T., Scimeca, J. C., Filloux, C., Peraldi, P., Carpentier, J. L., and Van Obberghen, E. (1993). J. Biol. Chem. 268, 9803–9810.

    PubMed  CAS  Google Scholar 

  48. Yan, C. Y. I. and Greene, L. A. (1998). J. Neurosci. 18, 4042–4049.

    PubMed  CAS  Google Scholar 

  49. Creedon, D. J., Johnson, E. M., and Lawrence, J. C. (1996). J. Biol. Chem. 271, 20,713–20,718.

    CAS  Google Scholar 

  50. Klesse, L. J., Meyers, K. A., Marshall, C. J., and Parada, L. F. (1999). Oncogene 18, 2055–2068.

    Article  PubMed  CAS  Google Scholar 

  51. Guyton, K. Z., Liu, Y., Gorospe, M., Xu, Q., and Holbrook, N. J. (1996). J. Biol. Chem. 271, 4138–4142.

    Article  PubMed  CAS  Google Scholar 

  52. Bi, R., Broutman, G., Foy, M. R., Thompson, R. F., and Baudry, M. (2000). Proc. Natl. Acad. Sci. USA. 97, 3602–3607.

    Article  PubMed  CAS  Google Scholar 

  53. Franke, T. F., Kaplan, D. R., and Cantley, L. C. (1997). Cell, 88, 435–437.

    Article  PubMed  CAS  Google Scholar 

  54. Yang, E., Zha, J., Jockel, J., Boise, L. H., Thompson, C. B., and Korsmeyer, S. J. (1995). Cell 80, 285–291.

    Article  PubMed  CAS  Google Scholar 

  55. Honda, K., Sawada, H., Kihara, T., Urushitani, M., Nakamizo, T., Akaike, A., and Shimohama, S. (2000). J. Neurosci. Res. 60, 321–327.

    Article  PubMed  CAS  Google Scholar 

  56. Zubenko, G. S., Stiffler, J. S., Hughes, H. B., and Martinez, A. J. (1999). Biol. Psychiatry 45, 731–736.

    Article  PubMed  CAS  Google Scholar 

  57. Edwards, D. P., Altmann, M., DeMarzo A., Zhang, Y., Weigel, N. L., and Beck, C. A. (1995). J. Steroid Biochem. Mol. Biol. 53, 449–458.

    Article  PubMed  CAS  Google Scholar 

  58. Beck, C. A., Zhang, Y., Weigel, N. L., and Edwards, D. P. (1996). J. Biol. Chem. 271, 1209–1217.

    Article  PubMed  CAS  Google Scholar 

  59. Behl, C., Trapp, T., Skutella, T., and Holsboer, F. (1997). Eur. J. Neurosci. 9, 912–920.

    Article  PubMed  CAS  Google Scholar 

  60. Tang, M. X., Jacobs, D., Stern, Y., Marder, K., Schofield, P., Gurland, B., Andrews, H., and Mayeux, R. (1996). Lancet 348, 429–432.

    Article  PubMed  CAS  Google Scholar 

  61. Singh, M., Meyer, E. M., and Simpkins, J. W. (1995). Endocrinology 136, 2320–2324.

    Article  PubMed  CAS  Google Scholar 

  62. Sohrabji, F., Miranda, R. C., and Toran-Allerand, C. D. (1995). Proc. Natl. Acad. Sci. USA 92, 11,110–11,114.

    Article  CAS  Google Scholar 

  63. Gahwiler, B. (1981). J. Neurosci. Methods 4, 329–342.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Center for Reproductive Sciences, Columbia University, College of Physicians and Surgeons, New York, NY

    Meharvan Singh PhD

  2. Department of Obstrics and Gynecology, Columbia University, College of Physicians and Surgeons, 650 West 168th Street, Black Building 1615, 10032, New York, NY

    Meharvan Singh PhD

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Correspondence to Meharvan Singh PhD.

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Singh, M. Ovarian hormones elicit phosphorylation of akt and extracellular-signal regulated kinase in explants of the cerebral cortex. Endocr 14, 407–415 (2001). https://doi.org/10.1385/ENDO:14:3:407

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  • DOI: https://doi.org/10.1385/ENDO:14:3:407

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